Induction of Class I Major Histocompatibility Complex Antigens in Human Teratocarcinoma Cells by Interferon without Induction of Differentiation, Growth Inhibition, or Resistance to Viral Infection1

The behavior of human teratocarcinoma cells, and especially their stem cells (embryonal carcinoma cells), may provide insights into the properties of human early embryonic cells. We report here that human recombinant •y-interferon (IFN-7) induced the expression of major histocompatibility complex Class I (HLA-A, B, C) antigens and /32-microglobulin in the two human embryonal carcinoma cell lines, 21021 p cl.4D3 and NTERA-2 11.1)1,and in the yolk sac carcinoma cell line, 141IH; human recombinant IFN-a and IFN-/8 were less effective inducers of these cell surface molecules. No induction was observed in the gestational choriocarcinoma cell line, JAR. Neither IFN-a, IFN-0, nor IFN-7 caused growth inhibition, expression of major histocompatibility complex Class II (HLA-DR) antigens, resistance to viral (vesicular stomatitis virus) infection, or expression of 2',5'-oligo(A)synthetase in any of the cells. Also, IFN-7 neither induced differentiation of NTERA-2 cl.Dl cells, which are pluripotent human stem cells, nor influenced their differentia tion induced by retinoic acid. However, developmental regulation of responsiveness to IFN was evident, since IFN-7 induced higher levels of surface expression of HLA-A, B, C and ^-microglobulin in the retinoic acid-induced differentiated NTERA-2 cl.Dl ceils than in the undifferentiated parental cells. Also, 2',5'-oligo(A)synthetase was inducible in the NTERA-2 cl.Dl differentiated cells by IFN-a and -/<,although not by IFN-7, and slight resistance to vesicular stomatitis virus infection was evident in aged cultures of differentiated cells exposed to IFN-a. The effect of recombinant mouse IFN-7 on major histocompatibility complex expression by several murine teratocarcinoma cells was also examined: H-2 Class I (H-2D11),but not class II (I-Ab), antigens were induced in the parietal yolk sac carcinoma lines, PYS and F9Ac cl.9; in cultures of PCC3/A/1 containing both embryonal carcinoma (EC) and differentiated cells; and in cultures of the EC cells, PCC4azaR and PCC4AO, without evidence of differentiation. No induction was observed in the murine EC cell lines, F9 or FA (H-2Kk). Our results indicate that human EC cells, like murine EC cells, exhibit only a partial response to the interferons, and that the extent of this response is developmentally regulated.